SK13082002A3 - Substituované beta-karbolíny, spôsob ich prípravy a farmaceutické prostriedky, ktoré ich obsahujú - Google Patents
Substituované beta-karbolíny, spôsob ich prípravy a farmaceutické prostriedky, ktoré ich obsahujú Download PDFInfo
- Publication number
- SK13082002A3 SK13082002A3 SK1308-2002A SK13082002A SK13082002A3 SK 13082002 A3 SK13082002 A3 SK 13082002A3 SK 13082002 A SK13082002 A SK 13082002A SK 13082002 A3 SK13082002 A3 SK 13082002A3
- Authority
- SK
- Slovakia
- Prior art keywords
- alkyl
- group
- phenyl
- carbon atoms
- mono
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 13
- 238000000034 method Methods 0.000 title claims description 10
- 230000008569 process Effects 0.000 title claims description 8
- AIFRHYZBTHREPW-UHFFFAOYSA-N β-carboline Chemical class N1=CC=C2C3=CC=CC=C3NC2=C1 AIFRHYZBTHREPW-UHFFFAOYSA-N 0.000 title abstract description 16
- 239000008194 pharmaceutical composition Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 114
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 19
- 208000035475 disorder Diseases 0.000 claims abstract description 15
- 239000003814 drug Substances 0.000 claims abstract description 14
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 427
- 125000004432 carbon atom Chemical group C* 0.000 claims description 234
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 180
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 118
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 92
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 89
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 76
- 229910052739 hydrogen Inorganic materials 0.000 claims description 68
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 62
- 239000001257 hydrogen Substances 0.000 claims description 59
- 229930192474 thiophene Natural products 0.000 claims description 59
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 58
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 58
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 58
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 claims description 58
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 56
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 46
- 125000001424 substituent group Chemical group 0.000 claims description 46
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 43
- 125000000623 heterocyclic group Chemical group 0.000 claims description 41
- -1 cyano, nitro, amino Chemical group 0.000 claims description 39
- 229910052757 nitrogen Inorganic materials 0.000 claims description 39
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 38
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 37
- 125000006413 ring segment Chemical group 0.000 claims description 37
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 claims description 33
- CIISBYKBBMFLEZ-UHFFFAOYSA-N 1,2-oxazolidine Chemical compound C1CNOC1 CIISBYKBBMFLEZ-UHFFFAOYSA-N 0.000 claims description 31
- WEQPBCSPRXFQQS-UHFFFAOYSA-N 4,5-dihydro-1,2-oxazole Chemical compound C1CC=NO1 WEQPBCSPRXFQQS-UHFFFAOYSA-N 0.000 claims description 30
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 29
- USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 claims description 29
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 29
- CZSRXHJVZUBEGW-UHFFFAOYSA-N 1,2-thiazolidine Chemical compound C1CNSC1 CZSRXHJVZUBEGW-UHFFFAOYSA-N 0.000 claims description 28
- VSWICNJIUPRZIK-UHFFFAOYSA-N 2-piperideine Chemical compound C1CNC=CC1 VSWICNJIUPRZIK-UHFFFAOYSA-N 0.000 claims description 28
- 125000005843 halogen group Chemical group 0.000 claims description 27
- GUUULVAMQJLDSY-UHFFFAOYSA-N 4,5-dihydro-1,2-thiazole Chemical compound C1CC=NS1 GUUULVAMQJLDSY-UHFFFAOYSA-N 0.000 claims description 25
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 24
- 229910052736 halogen Inorganic materials 0.000 claims description 24
- 150000002367 halogens Chemical class 0.000 claims description 23
- 125000004076 pyridyl group Chemical group 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 23
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
- 239000000460 chlorine Substances 0.000 claims description 20
- 229910052799 carbon Inorganic materials 0.000 claims description 15
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 15
- 229910052801 chlorine Inorganic materials 0.000 claims description 14
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 12
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 12
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical group C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims description 10
- 125000004429 atom Chemical group 0.000 claims description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
- 230000002265 prevention Effects 0.000 claims description 9
- 206010003246 arthritis Diseases 0.000 claims description 8
- 208000030507 AIDS Diseases 0.000 claims description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 7
- 201000008482 osteoarthritis Diseases 0.000 claims description 7
- 208000024827 Alzheimer disease Diseases 0.000 claims description 6
- 206010040070 Septic Shock Diseases 0.000 claims description 6
- 208000006673 asthma Diseases 0.000 claims description 6
- 238000004587 chromatography analysis Methods 0.000 claims description 6
- 208000015181 infectious disease Diseases 0.000 claims description 6
- 208000010125 myocardial infarction Diseases 0.000 claims description 6
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 6
- 201000001320 Atherosclerosis Diseases 0.000 claims description 5
- 206010006895 Cachexia Diseases 0.000 claims description 5
- 206010028980 Neoplasm Diseases 0.000 claims description 5
- 201000011510 cancer Diseases 0.000 claims description 5
- 231100000433 cytotoxic Toxicity 0.000 claims description 5
- 230000001472 cytotoxic effect Effects 0.000 claims description 5
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 4
- 206010017533 Fungal infection Diseases 0.000 claims description 4
- 206010061218 Inflammation Diseases 0.000 claims description 4
- 206010040047 Sepsis Diseases 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 4
- 230000004054 inflammatory process Effects 0.000 claims description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- 230000036303 septic shock Effects 0.000 claims description 4
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 claims description 3
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 3
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 3
- 241000701022 Cytomegalovirus Species 0.000 claims description 3
- 201000005569 Gout Diseases 0.000 claims description 3
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 3
- 150000007513 acids Chemical class 0.000 claims description 3
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 3
- 150000001413 amino acids Chemical class 0.000 claims description 3
- 230000015572 biosynthetic process Effects 0.000 claims description 3
- 125000001246 bromo group Chemical group Br* 0.000 claims description 3
- 230000006378 damage Effects 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 2
- 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 2
- 208000006386 Bone Resorption Diseases 0.000 claims description 2
- 201000009030 Carcinoma Diseases 0.000 claims description 2
- 206010063094 Cerebral malaria Diseases 0.000 claims description 2
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 2
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 2
- 208000011231 Crohn disease Diseases 0.000 claims description 2
- 208000037487 Endotoxemia Diseases 0.000 claims description 2
- 230000005526 G1 to G0 transition Effects 0.000 claims description 2
- 208000009329 Graft vs Host Disease Diseases 0.000 claims description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 2
- 206010024229 Leprosy Diseases 0.000 claims description 2
- 206010025323 Lymphomas Diseases 0.000 claims description 2
- 206010027236 Meningitis fungal Diseases 0.000 claims description 2
- 208000000112 Myalgia Diseases 0.000 claims description 2
- 208000031888 Mycoses Diseases 0.000 claims description 2
- 208000030852 Parasitic disease Diseases 0.000 claims description 2
- 201000004681 Psoriasis Diseases 0.000 claims description 2
- 206010037660 Pyrexia Diseases 0.000 claims description 2
- 208000033464 Reiter syndrome Diseases 0.000 claims description 2
- 206010063837 Reperfusion injury Diseases 0.000 claims description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims description 2
- 206010039491 Sarcoma Diseases 0.000 claims description 2
- 208000000453 Skin Neoplasms Diseases 0.000 claims description 2
- 206010048873 Traumatic arthritis Diseases 0.000 claims description 2
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 2
- 208000036142 Viral infection Diseases 0.000 claims description 2
- 208000027418 Wounds and injury Diseases 0.000 claims description 2
- 230000002378 acidificating effect Effects 0.000 claims description 2
- 239000000654 additive Substances 0.000 claims description 2
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 2
- 230000006907 apoptotic process Effects 0.000 claims description 2
- 230000002917 arthritic effect Effects 0.000 claims description 2
- 230000024279 bone resorption Effects 0.000 claims description 2
- 238000001212 derivatisation Methods 0.000 claims description 2
- 206010012601 diabetes mellitus Diseases 0.000 claims description 2
- 201000006549 dyspepsia Diseases 0.000 claims description 2
- 201000010056 fungal meningitis Diseases 0.000 claims description 2
- 208000024908 graft versus host disease Diseases 0.000 claims description 2
- 208000024798 heartburn Diseases 0.000 claims description 2
- 208000027866 inflammatory disease Diseases 0.000 claims description 2
- 208000014674 injury Diseases 0.000 claims description 2
- 208000018937 joint inflammation Diseases 0.000 claims description 2
- 208000032839 leukemia Diseases 0.000 claims description 2
- 208000022766 lymph node neoplasm Diseases 0.000 claims description 2
- 201000004792 malaria Diseases 0.000 claims description 2
- 230000036210 malignancy Effects 0.000 claims description 2
- 201000006417 multiple sclerosis Diseases 0.000 claims description 2
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 2
- 230000002018 overexpression Effects 0.000 claims description 2
- 208000024981 pyrosis Diseases 0.000 claims description 2
- 208000002574 reactive arthritis Diseases 0.000 claims description 2
- 231100000241 scar Toxicity 0.000 claims description 2
- 201000004595 synovitis Diseases 0.000 claims description 2
- 201000008827 tuberculosis Diseases 0.000 claims description 2
- 241001529453 unidentified herpesvirus Species 0.000 claims description 2
- 241000712461 unidentified influenza virus Species 0.000 claims description 2
- 230000009385 viral infection Effects 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 10
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims 2
- 208000014644 Brain disease Diseases 0.000 claims 1
- 208000003322 Coinfection Diseases 0.000 claims 1
- 201000001263 Psoriatic Arthritis Diseases 0.000 claims 1
- 208000036824 Psoriatic arthropathy Diseases 0.000 claims 1
- 201000010001 Silicosis Diseases 0.000 claims 1
- 241000580858 Simian-Human immunodeficiency virus Species 0.000 claims 1
- 230000000996 additive effect Effects 0.000 claims 1
- 208000029028 brain injury Diseases 0.000 claims 1
- 125000004122 cyclic group Chemical group 0.000 claims 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
- 125000002346 iodo group Chemical group I* 0.000 claims 1
- 230000003387 muscular Effects 0.000 claims 1
- 229960002262 profenamine Drugs 0.000 claims 1
- 201000003651 pulmonary sarcoidosis Diseases 0.000 claims 1
- 201000005404 rubella Diseases 0.000 claims 1
- 208000011571 secondary malignant neoplasm Diseases 0.000 claims 1
- 238000000926 separation method Methods 0.000 claims 1
- 230000009772 tissue formation Effects 0.000 claims 1
- 241000701161 unidentified adenovirus Species 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 14
- 102000001284 I-kappa-B kinase Human genes 0.000 abstract description 13
- 108060006678 I-kappa-B kinase Proteins 0.000 abstract description 13
- 238000011321 prophylaxis Methods 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 106
- 239000000243 solution Substances 0.000 description 78
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 72
- 239000000047 product Substances 0.000 description 72
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 72
- 239000011541 reaction mixture Substances 0.000 description 58
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
- 239000000203 mixture Substances 0.000 description 45
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 40
- 235000019439 ethyl acetate Nutrition 0.000 description 36
- 239000012043 crude product Substances 0.000 description 34
- 229940093499 ethyl acetate Drugs 0.000 description 34
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
- 238000003756 stirring Methods 0.000 description 25
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 22
- 150000002431 hydrogen Chemical class 0.000 description 21
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 239000000741 silica gel Substances 0.000 description 18
- 229910002027 silica gel Inorganic materials 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
- 229920006395 saturated elastomer Polymers 0.000 description 17
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 125000003118 aryl group Chemical group 0.000 description 15
- 239000012267 brine Substances 0.000 description 15
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 13
- 239000012044 organic layer Substances 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
- 108091000080 Phosphotransferase Proteins 0.000 description 7
- 102000020233 phosphotransferase Human genes 0.000 description 7
- 150000003254 radicals Chemical class 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- 125000000547 substituted alkyl group Chemical group 0.000 description 7
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 125000003107 substituted aryl group Chemical group 0.000 description 6
- 239000008096 xylene Substances 0.000 description 6
- 239000007995 HEPES buffer Substances 0.000 description 5
- 125000003545 alkoxy group Chemical group 0.000 description 5
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
- 238000002953 preparative HPLC Methods 0.000 description 5
- 150000003738 xylenes Chemical class 0.000 description 5
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 4
- QIIQCUUHBSIRSM-UHFFFAOYSA-N 7-bromo-9h-pyrido[3,4-b]indole Chemical compound N1=CC=C2C3=CC=C(Br)C=C3NC2=C1 QIIQCUUHBSIRSM-UHFFFAOYSA-N 0.000 description 4
- BXNJHAXVSOCGBA-UHFFFAOYSA-N Harmine Chemical compound N1=CC=C2C3=CC=C(OC)C=C3NC2=C1C BXNJHAXVSOCGBA-UHFFFAOYSA-N 0.000 description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
- 101150091206 Nfkbia gene Proteins 0.000 description 4
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 229960003966 nicotinamide Drugs 0.000 description 4
- 239000011570 nicotinamide Substances 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 3
- LMDPJJFWLNRVEH-UHFFFAOYSA-N Norharmine Natural products N1=CC=C2C3=CC=C(OC)C=C3NC2=C1 LMDPJJFWLNRVEH-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 229910017604 nitric acid Inorganic materials 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
- VOCGEKMEZOPDFP-UHFFFAOYSA-N 2-(6-methoxy-1h-indol-3-yl)ethanamine Chemical compound COC1=CC=C2C(CCN)=CNC2=C1 VOCGEKMEZOPDFP-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- JTEJPPKMYBDEMY-UHFFFAOYSA-N 5-methoxytryptamine Chemical compound COC1=CC=C2NC=C(CCN)C2=C1 JTEJPPKMYBDEMY-UHFFFAOYSA-N 0.000 description 2
- SVQAMMNMCFBVEQ-UHFFFAOYSA-N 7-chloro-8-methoxy-9h-pyrido[3,4-b]indole Chemical compound C12=CC=NC=C2NC2=C1C=CC(Cl)=C2OC SVQAMMNMCFBVEQ-UHFFFAOYSA-N 0.000 description 2
- XMTAVUKXUXYLEN-UHFFFAOYSA-N 9-chloro-8-methoxypyrido[3,4-b]indole;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C12=CC=NC=C2N(Cl)C2=C1C=CC=C2OC XMTAVUKXUXYLEN-UHFFFAOYSA-N 0.000 description 2
- 206010001513 AIDS related complex Diseases 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- DHCLVCXQIBBOPH-UHFFFAOYSA-N Glycerol 2-phosphate Chemical compound OCC(CO)OP(O)(O)=O DHCLVCXQIBBOPH-UHFFFAOYSA-N 0.000 description 2
- RERZNCLIYCABFS-UHFFFAOYSA-N Harmaline hydrochloride Natural products C1CN=C(C)C2=C1C1=CC=C(OC)C=C1N2 RERZNCLIYCABFS-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
- DFPAKSUCGFBDDF-ZQBYOMGUSA-N [14c]-nicotinamide Chemical compound N[14C](=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-ZQBYOMGUSA-N 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- MXMOTZIXVICDSD-UHFFFAOYSA-N anisoyl chloride Chemical compound COC1=CC=C(C(Cl)=O)C=C1 MXMOTZIXVICDSD-UHFFFAOYSA-N 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 150000005840 aryl radicals Chemical group 0.000 description 2
- 239000012131 assay buffer Substances 0.000 description 2
- 229960002685 biotin Drugs 0.000 description 2
- 235000020958 biotin Nutrition 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 108010073357 cyanoginosin LR Proteins 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- PSFDQSOCUJVVGF-UHFFFAOYSA-N harman Chemical compound C12=CC=CC=C2NC2=C1C=CN=C2C PSFDQSOCUJVVGF-UHFFFAOYSA-N 0.000 description 2
- VJHLDRVYTQNASM-UHFFFAOYSA-N harmine Natural products CC1=CN=CC=2NC3=CC(=CC=C3C=21)OC VJHLDRVYTQNASM-UHFFFAOYSA-N 0.000 description 2
- 150000007857 hydrazones Chemical class 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- ZYZCGGRZINLQBL-GWRQVWKTSA-N microcystin-LR Chemical compound C([C@H](OC)[C@@H](C)\C=C(/C)\C=C\[C@H]1[C@@H](C(=O)N[C@H](CCC(=O)N(C)C(=C)C(=O)N[C@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]([C@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1)C(O)=O)C(O)=O)C)C1=CC=CC=C1 ZYZCGGRZINLQBL-GWRQVWKTSA-N 0.000 description 2
- DIDLWIPCWUSYPF-UHFFFAOYSA-N microcystin-LR Natural products COC(Cc1ccccc1)C(C)C=C(/C)C=CC2NC(=O)C(NC(CCCNC(=N)N)C(=O)O)NC(=O)C(C)C(NC(=O)C(NC(CC(C)C)C(=O)O)NC(=O)C(C)NC(=O)C(=C)N(C)C(=O)CCC(NC(=O)C2C)C(=O)O)C(=O)O DIDLWIPCWUSYPF-UHFFFAOYSA-N 0.000 description 2
- MAJWMVWXSBFTOR-UHFFFAOYSA-N n-(7-chloropyrido[3,4-b]indol-9-yl)benzamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C(Cl)=CC=C(C2=CC=NC=C22)C=1N2NC(=O)C1=CC=CC=C1 MAJWMVWXSBFTOR-UHFFFAOYSA-N 0.000 description 2
- 235000005152 nicotinamide Nutrition 0.000 description 2
- MOOYVEVEDVVKGD-UHFFFAOYSA-N oxaldehydic acid;hydrate Chemical compound O.OC(=O)C=O MOOYVEVEDVVKGD-UHFFFAOYSA-N 0.000 description 2
- 239000002831 pharmacologic agent Substances 0.000 description 2
- BSCCSDNZEIHXOK-UHFFFAOYSA-N phenyl carbamate Chemical compound NC(=O)OC1=CC=CC=C1 BSCCSDNZEIHXOK-UHFFFAOYSA-N 0.000 description 2
- 150000003904 phospholipids Chemical class 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 230000000770 proinflammatory effect Effects 0.000 description 2
- 230000017854 proteolysis Effects 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- YJBKVPRVZAQTPY-UHFFFAOYSA-J tetrachlorostannane;dihydrate Chemical compound O.O.Cl[Sn](Cl)(Cl)Cl YJBKVPRVZAQTPY-UHFFFAOYSA-J 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical class C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 description 2
- LMFPPUVGWDZXMB-UHFFFAOYSA-N (4-propan-2-ylphenyl)hydrazine;hydrochloride Chemical compound Cl.CC(C)C1=CC=C(NN)C=C1 LMFPPUVGWDZXMB-UHFFFAOYSA-N 0.000 description 1
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
- NMOCOWABJRWQGY-UHFFFAOYSA-N 2-(4,4-diethoxybutyl)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CCCC(OCC)OCC)C(=O)C2=C1 NMOCOWABJRWQGY-UHFFFAOYSA-N 0.000 description 1
- YZAWADGJXKCLTI-UHFFFAOYSA-N 2-(5-fluoro-1h-indol-3-yl)ethanamine;hydrochloride Chemical compound Cl.C1=C(F)C=C2C(CCN)=CNC2=C1 YZAWADGJXKCLTI-UHFFFAOYSA-N 0.000 description 1
- BQTOKMYKZPCPRW-UHFFFAOYSA-N 2-(6-fluoro-1h-indol-3-yl)ethanamine Chemical compound FC1=CC=C2C(CCN)=CNC2=C1 BQTOKMYKZPCPRW-UHFFFAOYSA-N 0.000 description 1
- NIZPWFMKGBLCAW-UHFFFAOYSA-N 2-(6-propan-2-yl-1h-indol-3-yl)ethanamine;hydrochloride Chemical compound Cl.CC(C)C1=CC=C2C(CCN)=CNC2=C1 NIZPWFMKGBLCAW-UHFFFAOYSA-N 0.000 description 1
- IHZLYRJLSJTGST-UHFFFAOYSA-N 2-fluorobenzamide;hydrochloride Chemical compound Cl.NC(=O)C1=CC=CC=C1F IHZLYRJLSJTGST-UHFFFAOYSA-N 0.000 description 1
- JJKWHOSQTYYFAE-UHFFFAOYSA-N 2-methoxyacetyl chloride Chemical compound COCC(Cl)=O JJKWHOSQTYYFAE-UHFFFAOYSA-N 0.000 description 1
- ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 1
- KBJOWLXMHIWJCM-UHFFFAOYSA-N 2-methylpyrido[3,4-b]indol-8-ol Chemical compound OC1=CC=CC2=C3C=CN(C)C=C3N=C21 KBJOWLXMHIWJCM-UHFFFAOYSA-N 0.000 description 1
- UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-tetramethylbenzidine Chemical compound CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 description 1
- UZGLOGCJCWBBIV-UHFFFAOYSA-N 3-(chloromethyl)pyridin-1-ium;chloride Chemical compound Cl.ClCC1=CC=CN=C1 UZGLOGCJCWBBIV-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- RYKLZUPYJFFNRR-UHFFFAOYSA-N 3-hydroxypiperidin-2-one Chemical compound OC1CCCNC1=O RYKLZUPYJFFNRR-UHFFFAOYSA-N 0.000 description 1
- RUQIUASLAXJZIE-UHFFFAOYSA-N 3-methoxybenzoyl chloride Chemical compound COC1=CC=CC(C(Cl)=O)=C1 RUQIUASLAXJZIE-UHFFFAOYSA-N 0.000 description 1
- ISULZYQDGYXDFW-UHFFFAOYSA-N 3-methylbutanoyl chloride Chemical compound CC(C)CC(Cl)=O ISULZYQDGYXDFW-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- PXACTUVBBMDKRW-UHFFFAOYSA-N 4-bromobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Br)C=C1 PXACTUVBBMDKRW-UHFFFAOYSA-N 0.000 description 1
- CZKLEJHVLCMVQR-UHFFFAOYSA-N 4-fluorobenzoyl chloride Chemical compound FC1=CC=C(C(Cl)=O)C=C1 CZKLEJHVLCMVQR-UHFFFAOYSA-N 0.000 description 1
- BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 1
- 229940097276 5-methoxytryptamine Drugs 0.000 description 1
- NFQUVOWXTZAMHA-UHFFFAOYSA-N 6,8-dibromo-7-methoxy-9h-pyrido[3,4-b]indole Chemical compound C1=NC=C2NC3=C(Br)C(OC)=C(Br)C=C3C2=C1 NFQUVOWXTZAMHA-UHFFFAOYSA-N 0.000 description 1
- FMEBIWNKYZUWFV-UHFFFAOYSA-N 6-chloropyridine-3-carbonyl chloride Chemical compound ClC(=O)C1=CC=C(Cl)N=C1 FMEBIWNKYZUWFV-UHFFFAOYSA-N 0.000 description 1
- FQORTJVTWJEMDJ-UHFFFAOYSA-N 7,9-dichloro-8-methoxypyrido[3,4-b]indole;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C12=CC=NC=C2N(Cl)C2=C1C=CC(Cl)=C2OC FQORTJVTWJEMDJ-UHFFFAOYSA-N 0.000 description 1
- NCYAFHRISIDMCX-UHFFFAOYSA-N 7-(trifluoromethyl)-2,3,4,9-tetrahydro-1h-pyrido[3,4-b]indole Chemical compound C1CNCC2=C1C1=CC=C(C(F)(F)F)C=C1N2 NCYAFHRISIDMCX-UHFFFAOYSA-N 0.000 description 1
- FNEDMIBOPWKKPY-UHFFFAOYSA-N 7-chloro-8-fluoro-9h-pyrido[3,4-b]indole;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C12=CC=NC=C2NC2=C1C=CC(Cl)=C2F FNEDMIBOPWKKPY-UHFFFAOYSA-N 0.000 description 1
- CZIASKQYBGOYRW-UHFFFAOYSA-N 7-chloro-8-methoxy-9-nitropyrido[3,4-b]indole Chemical compound C12=CC=NC=C2N([N+]([O-])=O)C2=C1C=CC(Cl)=C2OC CZIASKQYBGOYRW-UHFFFAOYSA-N 0.000 description 1
- GMFVPTJVBPCULC-UHFFFAOYSA-N 7-chloro-9-nitropyrido[3,4-b]indole Chemical compound C1=C(Cl)C=C2N([N+](=O)[O-])C3=CN=CC=C3C2=C1 GMFVPTJVBPCULC-UHFFFAOYSA-N 0.000 description 1
- MQEOFUKOSJJCPH-UHFFFAOYSA-N 7-chloro-9h-pyrido[3,4-b]indole Chemical compound N1=CC=C2C3=CC=C(Cl)C=C3NC2=C1 MQEOFUKOSJJCPH-UHFFFAOYSA-N 0.000 description 1
- HOTOILFEHUMZBO-UHFFFAOYSA-N 7-chloro-n,n-dimethylpyrido[3,4-b]indol-9-amine;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=C(Cl)C=C2N(N(C)C)C3=CN=CC=C3C2=C1 HOTOILFEHUMZBO-UHFFFAOYSA-N 0.000 description 1
- MVHWKWPTMPHNME-UHFFFAOYSA-N 7-chloro-n-methylpyrido[3,4-b]indol-9-amine Chemical compound C1=C(Cl)C=C2N(NC)C3=CN=CC=C3C2=C1 MVHWKWPTMPHNME-UHFFFAOYSA-N 0.000 description 1
- UQYVODUEKNJJDJ-UHFFFAOYSA-N 7-chloropyrido[3,4-b]indol-9-amine Chemical compound C1=C(Cl)C=C2N(N)C3=CN=CC=C3C2=C1 UQYVODUEKNJJDJ-UHFFFAOYSA-N 0.000 description 1
- UYANBQJGGHZYGM-UHFFFAOYSA-N 7-ethoxy-2-methylpyrido[3,4-b]indole Chemical compound CN1C=CC2=C3C=CC(OCC)=CC3=NC2=C1 UYANBQJGGHZYGM-UHFFFAOYSA-N 0.000 description 1
- AUPDLGPLWDFZFL-UHFFFAOYSA-N 7-fluoro-9h-pyrido[3,4-b]indole Chemical compound N1=CC=C2C3=CC=C(F)C=C3NC2=C1 AUPDLGPLWDFZFL-UHFFFAOYSA-N 0.000 description 1
- QANFYAPQAFFWIA-UHFFFAOYSA-N 7-propan-2-yl-9h-pyrido[3,4-b]indole Chemical compound N1=CC=C2C3=CC=C(C(C)C)C=C3NC2=C1 QANFYAPQAFFWIA-UHFFFAOYSA-N 0.000 description 1
- VCBQWVILQXIWIS-UHFFFAOYSA-N 7-propan-2-yl-9h-pyrido[3,4-b]indole;hydrochloride Chemical compound Cl.N1=CC=C2C3=CC=C(C(C)C)C=C3NC2=C1 VCBQWVILQXIWIS-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- MVVBZSKABMCEIO-UHFFFAOYSA-N 8-fluoro-9h-pyrido[3,4-b]indole Chemical compound C12=CC=NC=C2NC2=C1C=CC=C2F MVVBZSKABMCEIO-UHFFFAOYSA-N 0.000 description 1
- CIEVLKSHXKXRQR-UHFFFAOYSA-N 8-methoxy-9h-pyrido[3,4-b]indole Chemical compound C12=CC=NC=C2NC2=C1C=CC=C2OC CIEVLKSHXKXRQR-UHFFFAOYSA-N 0.000 description 1
- DGXHZCLGTXOEMW-UHFFFAOYSA-N 9h-pyrido[3,4-b]indole-7-carbonitrile Chemical compound N1=CC=C2C3=CC=C(C#N)C=C3NC2=C1 DGXHZCLGTXOEMW-UHFFFAOYSA-N 0.000 description 1
- DMUTUWPUYAJHGO-UHFFFAOYSA-N 9h-pyrido[3,4-b]indole-7-carboxylic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N1=CC=C2C3=CC=C(C(=O)O)C=C3NC2=C1 DMUTUWPUYAJHGO-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 108010029697 CD40 Ligand Proteins 0.000 description 1
- 102100032937 CD40 ligand Human genes 0.000 description 1
- 102100032218 Cytokine-inducible SH2-containing protein Human genes 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 108010016626 Dipeptides Proteins 0.000 description 1
- 206010014824 Endotoxic shock Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010018634 Gouty Arthritis Diseases 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- 101000943420 Homo sapiens Cytokine-inducible SH2-containing protein Proteins 0.000 description 1
- 101000979342 Homo sapiens Nuclear factor NF-kappa-B p105 subunit Proteins 0.000 description 1
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- JZRMBDHPALEPDM-UHFFFAOYSA-N N-(6-Chloro-9H-pyrido[3,4-b]indol-8-yl)-3-pyridinecarboxamide Chemical compound C=12NC3=CN=CC=C3C2=CC(Cl)=CC=1NC(=O)C1=CC=CN=C1 JZRMBDHPALEPDM-UHFFFAOYSA-N 0.000 description 1
- UHOMRQYMQQZPKK-UHFFFAOYSA-N N-(7-chloropyrido[3,4-b]indol-9-yl)-4-methoxybenzamide 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC(OC)=CC=C1C(=O)NN1C2=CC(Cl)=CC=C2C2=CC=NC=C21 UHOMRQYMQQZPKK-UHFFFAOYSA-N 0.000 description 1
- FPYKHALNVBFXQE-UHFFFAOYSA-N N-(7-chloropyrido[3,4-b]indol-9-yl)propanamide 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=C(Cl)C=C2N(NC(=O)CC)C3=CN=CC=C3C2=C1 FPYKHALNVBFXQE-UHFFFAOYSA-N 0.000 description 1
- LVDRREOUMKACNJ-BKMJKUGQSA-N N-[(2R,3S)-2-(4-chlorophenyl)-1-(1,4-dimethyl-2-oxoquinolin-7-yl)-6-oxopiperidin-3-yl]-2-methylpropane-1-sulfonamide Chemical compound CC(C)CS(=O)(=O)N[C@H]1CCC(=O)N([C@@H]1c1ccc(Cl)cc1)c1ccc2c(C)cc(=O)n(C)c2c1 LVDRREOUMKACNJ-BKMJKUGQSA-N 0.000 description 1
- 102100023050 Nuclear factor NF-kappa-B p105 subunit Human genes 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 235000019486 Sunflower oil Nutrition 0.000 description 1
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 206010044248 Toxic shock syndrome Diseases 0.000 description 1
- 231100000650 Toxic shock syndrome Toxicity 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- SPXSEZMVRJLHQG-XMMPIXPASA-N [(2R)-1-[[4-[(3-phenylmethoxyphenoxy)methyl]phenyl]methyl]pyrrolidin-2-yl]methanol Chemical compound C(C1=CC=CC=C1)OC=1C=C(OCC2=CC=C(CN3[C@H](CCC3)CO)C=C2)C=CC=1 SPXSEZMVRJLHQG-XMMPIXPASA-N 0.000 description 1
- DBNLGTYGKCMLLR-UHFFFAOYSA-N [4-(trifluoromethyl)phenyl]hydrazine Chemical compound NNC1=CC=C(C(F)(F)F)C=C1 DBNLGTYGKCMLLR-UHFFFAOYSA-N 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 1
- 239000001099 ammonium carbonate Substances 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- GETQZCLCWQTVFV-UHFFFAOYSA-N anhydrous trimethylamine Natural products CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000002424 anti-apoptotic effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical group 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 229940127271 compound 49 Drugs 0.000 description 1
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 230000000139 costimulatory effect Effects 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 230000001085 cytostatic effect Effects 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 1
- 229950006137 dexfosfoserine Drugs 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000002845 discoloration Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 235000021323 fish oil Nutrition 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- MSYBLBLAMDYKKZ-UHFFFAOYSA-N hydron;pyridine-3-carbonyl chloride;chloride Chemical compound Cl.ClC(=O)C1=CC=CN=C1 MSYBLBLAMDYKKZ-UHFFFAOYSA-N 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 238000002650 immunosuppressive therapy Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- XMWFMEYDRNJSOO-UHFFFAOYSA-N morpholine-4-carbonyl chloride Chemical compound ClC(=O)N1CCOCC1 XMWFMEYDRNJSOO-UHFFFAOYSA-N 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- IFGGVAYYQUJSNT-UHFFFAOYSA-N n-(7-chloropyrido[3,4-b]indol-9-yl)-2-methoxyacetamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=C(Cl)C=C2N(NC(=O)COC)C3=CN=CC=C3C2=C1 IFGGVAYYQUJSNT-UHFFFAOYSA-N 0.000 description 1
- MWXOWEQBVZTVPP-UHFFFAOYSA-N n-(7-chloropyrido[3,4-b]indol-9-yl)-3-methylbutanamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=C(Cl)C=C2N(NC(=O)CC(C)C)C3=CN=CC=C3C2=C1 MWXOWEQBVZTVPP-UHFFFAOYSA-N 0.000 description 1
- VKDGQVWNUBSADA-UHFFFAOYSA-N n-(7-chloropyrido[3,4-b]indol-9-yl)-4-fluorobenzamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC(F)=CC=C1C(=O)NN1C2=CC(Cl)=CC=C2C2=CC=NC=C21 VKDGQVWNUBSADA-UHFFFAOYSA-N 0.000 description 1
- UMSBJGIEVORKBV-UHFFFAOYSA-N n-(7-chloropyrido[3,4-b]indol-9-yl)-n-methylacetamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=C(Cl)C=C2N(N(C(C)=O)C)C3=CN=CC=C3C2=C1 UMSBJGIEVORKBV-UHFFFAOYSA-N 0.000 description 1
- HQLPPNAFKHCUKI-UHFFFAOYSA-N n-(7-chloropyrido[3,4-b]indol-9-yl)methanesulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=C(Cl)C=C2N(NS(=O)(=O)C)C3=CN=CC=C3C2=C1 HQLPPNAFKHCUKI-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 108010087904 neutravidin Proteins 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 235000020030 perry Nutrition 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 1
- 229960004838 phosphoric acid Drugs 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
- 102000021127 protein binding proteins Human genes 0.000 description 1
- 108091011138 protein binding proteins Proteins 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000000552 rheumatic effect Effects 0.000 description 1
- 150000003873 salicylate salts Chemical class 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 235000011044 succinic acid Nutrition 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229940032330 sulfuric acid Drugs 0.000 description 1
- 239000002600 sunflower oil Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- RZWIIPASKMUIAC-VQTJNVASSA-N thromboxane Chemical compound CCCCCCCC[C@H]1OCCC[C@@H]1CCCCCCC RZWIIPASKMUIAC-VQTJNVASSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A61P31/06—Antibacterial agents for tuberculosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P33/06—Antimalarials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D241/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D498/14—Ortho-condensed systems
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Rheumatology (AREA)
- Virology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pulmonology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Diabetes (AREA)
- Immunology (AREA)
- Neurology (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Neurosurgery (AREA)
- Dermatology (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Cardiology (AREA)
- Hospice & Palliative Care (AREA)
- AIDS & HIV (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Psychiatry (AREA)
- Heart & Thoracic Surgery (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP00105514A EP1134221A1 (en) | 2000-03-15 | 2000-03-15 | Substituted beta-carbolines as lkB kinase inhibitors |
EP00125169A EP1209158A1 (en) | 2000-11-18 | 2000-11-18 | Substituted beta-carbolines |
PCT/EP2001/002237 WO2001068648A1 (en) | 2000-03-15 | 2001-02-28 | Substituted beta-carbolines with ikb-kinase inhibiting activity |
Publications (1)
Publication Number | Publication Date |
---|---|
SK13082002A3 true SK13082002A3 (sk) | 2003-04-01 |
Family
ID=26070675
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
SK1308-2002A SK13082002A3 (sk) | 2000-03-15 | 2001-02-28 | Substituované beta-karbolíny, spôsob ich prípravy a farmaceutické prostriedky, ktoré ich obsahujú |
Country Status (23)
Country | Link |
---|---|
US (3) | US6627637B2 (ru) |
JP (1) | JP5000828B2 (ru) |
KR (1) | KR100826817B1 (ru) |
CN (1) | CN100509810C (ru) |
AT (1) | ATE465161T1 (ru) |
AU (2) | AU3741801A (ru) |
BR (1) | BR0109161A (ru) |
CA (1) | CA2402549A1 (ru) |
CZ (1) | CZ301077B6 (ru) |
DE (1) | DE60141895D1 (ru) |
EE (1) | EE200200523A (ru) |
HK (1) | HK1054039B (ru) |
HR (1) | HRP20020748A2 (ru) |
HU (1) | HUP0300894A3 (ru) |
IL (2) | IL151695A0 (ru) |
ME (1) | MEP28108A (ru) |
MX (1) | MXPA02007981A (ru) |
NO (1) | NO324248B1 (ru) |
NZ (1) | NZ521386A (ru) |
PL (1) | PL357284A1 (ru) |
RU (1) | RU2277095C2 (ru) |
SK (1) | SK13082002A3 (ru) |
YU (1) | YU65502A (ru) |
Families Citing this family (49)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
PL357284A1 (en) * | 2000-03-15 | 2004-07-26 | Aventis Pharma Deutschland Gmbh | Substituted beta-carbolines with ikb-kinase inhibiting activity |
CZ20032287A3 (cs) * | 2001-02-01 | 2004-02-18 | Bristol-Myers Squibb Company | Způsoby léčení zánětlivých a imunitních nemocí za použití inhibitorů IkB kinázy (IKK) |
AU2002352498A1 (en) * | 2001-11-07 | 2003-05-19 | Millennium Pharmaceuticals, Inc. | Carboline derivatives as inhibitors of ikb in the treatment of multiple myeloma and others cancers |
US7462638B2 (en) * | 2002-08-17 | 2008-12-09 | Sanofi-Aventis Deutschland Gmbh | Use of IκB-kinase inhibitors in pain therapy |
US20040166095A1 (en) * | 2003-02-25 | 2004-08-26 | Blazar Bruce R. | Methods for preventing GVHD |
EA009121B1 (ru) * | 2003-04-09 | 2007-10-26 | Миллениум Фармасьютикалз, Инк. | Бета-карболины, применяемые для лечения воспалительных заболеваний |
BRPI0509660A (pt) * | 2004-04-09 | 2007-10-09 | Millennium Pharm Inc | compostos de beta-carbolina de utilidade no tratamento de doenças inflamatórias |
WO2006112549A1 (ja) * | 2005-04-20 | 2006-10-26 | Takeda Pharmaceutical Company Limited | 縮合複素環化合物 |
US8119655B2 (en) * | 2005-10-07 | 2012-02-21 | Takeda Pharmaceutical Company Limited | Kinase inhibitors |
ES2390135T3 (es) | 2005-11-22 | 2012-11-06 | Merck Sharp & Dohme Corp. | Compuestos tricíclicos útiles como inhibidores de quinasas |
US20090137579A1 (en) * | 2007-10-23 | 2009-05-28 | Millennium Pharmaceuticals, Inc. | Mesylate salt of an IKK inhibitor |
WO2009054965A1 (en) * | 2007-10-23 | 2009-04-30 | Millennium Pharmaceuticals, Inc. | Salts of n- (6-chloro-9h-pyrido [3,4-b] ind0l-8-yl) -4- [2- (2, 6-dimethyl-4-morpholinyl) -2-0x0e thyl] -6, 6-dimethyl-morpholinecarboxamide |
JP5537439B2 (ja) * | 2007-12-19 | 2014-07-02 | アムジエン・インコーポレーテツド | 細胞周期阻害剤としての縮合ピリジン、ピリミジンおよびトリアジン化合物 |
CA2727055C (en) | 2008-01-11 | 2016-12-20 | Albany Molecular Research, Inc. | (1-azinone) -substituted pyridoindoles as mch antagonists |
CN101245066B (zh) * | 2008-01-23 | 2010-11-10 | 复旦大学 | 一种制备7-烷氧基-2,9-二氮芴衍生物的方法 |
EP2278973B1 (en) * | 2008-04-07 | 2011-11-02 | Amgen Inc. | Gem-disubstituted and spirocyclic amino pyridines/pyrimidines as cell cycle inhibitors |
JP5892791B2 (ja) | 2008-05-14 | 2016-03-23 | ミレニアム ファーマシューティカルズ, インコーポレイテッドMillennium Pharmaceuticals, Inc. | 適応免疫における免疫調節物質の効果をモニターするための方法およびキット |
AR072092A1 (es) * | 2008-06-11 | 2010-08-04 | Genentech Inc | Diazacarbazoles y metodos de uso |
US20110124654A1 (en) * | 2008-06-11 | 2011-05-26 | Huifen Chen | Diazacarbazoles and methods of use |
US20100074939A1 (en) * | 2008-09-25 | 2010-03-25 | Osteogenex Inc. | Harmine compounds for promoting bone growth |
CN101717397B (zh) * | 2008-10-09 | 2012-11-28 | 中国科学院上海药物研究所 | 一类取代吡啶并[2',1':2,3]咪唑并[4,5-c]异喹啉酮类化合物及其合成方法和用途,以及包含该类化合物的药物组合物 |
US8618299B2 (en) | 2009-07-01 | 2013-12-31 | Albany Molecular Research, Inc. | Azinone-substituted azapolycycle MCH-1 antagonists, methods of making, and use thereof |
US9073925B2 (en) | 2009-07-01 | 2015-07-07 | Albany Molecular Research, Inc. | Azinone-substituted azabicycloalkane-indole and azabicycloalkane-pyrrolo-pyridine MCH-1 antagonists, methods of making, and use thereof |
EP2448585B1 (en) | 2009-07-01 | 2014-01-01 | Albany Molecular Research, Inc. | Azinone-substituted azepino[b]indole and pyrido-pyrrolo-azepine mch-1 antagonists, methods of making, and use thereof |
WO2011003007A1 (en) | 2009-07-01 | 2011-01-06 | Albany Molecular Research, Inc. | Azabicycloalkane-indole and azabicycloalkane-pyrrolo-pyridine mch-1 antagonists, methods of making, and use thereof |
US20110183938A1 (en) * | 2009-12-16 | 2011-07-28 | Genentech, Inc. | 1,7-diazacarbazoles and methods of use |
RU2419431C1 (ru) * | 2010-02-10 | 2011-05-27 | Андрей Александрович Винник | ПРОИЗВОДНЫЕ β-КАРБОЛИНА, ОБЛАДАЮЩИЕ ПРОТИВОТУБЕРКУЛЕЗНОЙ АКТИВНОСТЬЮ, ИХ ПРИМЕНЕНИЯ ДЛЯ ПРОИЗВОДСТВА ЛЕКАРСТВЕННОГО СРЕДСТВА, СПОСОБ ИХ СИНТЕЗА, А ТАКЖЕ НОВЫЕ МЕТОДЫ ЛЕЧЕНИЯ С ИХ ИСПОЛЬЗОВАНИЕМ |
US8685969B2 (en) | 2010-06-16 | 2014-04-01 | Bristol-Myers Squibb Company | Carboline carboxamide compounds useful as kinase inhibitors |
JP2013533239A (ja) * | 2010-06-25 | 2013-08-22 | ファキュルテ ユニヴェルシテール ノートル−ダム ド ラ ペ | 増殖性疾患の治療に有用なβカルボリン誘導体 |
EP2455378A1 (en) * | 2010-11-03 | 2012-05-23 | Philip Morris Products S.A. | Carbazole and carboline derivatives, and preparation and therapeutic applications thereof |
WO2012088124A2 (en) | 2010-12-21 | 2012-06-28 | Albany Molecular Research, Inc. | Tetrahydro-azacarboline mch-1 antagonists, methods of making, and uses thereof |
WO2012088038A2 (en) | 2010-12-21 | 2012-06-28 | Albany Molecular Research, Inc. | Piperazinone-substituted tetrahydro-carboline mch-1 antagonists, methods of making, and uses thereof |
JP5854492B2 (ja) * | 2011-02-24 | 2016-02-09 | 国立大学法人 岡山大学 | 軟骨細胞分化誘導促進剤 |
ES2620521T3 (es) | 2011-03-23 | 2017-06-28 | Amgen Inc. | Inhibidores duales tricíclicos condensados de CDK 4/6 y FLT3 |
CN102250089B (zh) * | 2011-05-20 | 2012-11-14 | 中国科学院南海海洋研究所 | β-咔啉生物碱及其在制备抗疟疾药物中的应用 |
WO2014153203A2 (en) | 2013-03-14 | 2014-09-25 | Ossifi Inc. | Alkyl-amine harmine derivatives for promoting bone growth |
TN2015000516A1 (en) * | 2013-05-28 | 2017-04-06 | Astrazeneca Ab | Chemical compounds |
JP6434968B2 (ja) * | 2013-07-02 | 2018-12-05 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | Rock阻害剤としての三環式ピリド−カルボキサミド誘導体 |
EP3016950B1 (en) * | 2013-07-02 | 2017-06-07 | Bristol-Myers Squibb Company | Tricyclic pyrido-carboxamide derivatives as rock inhibitors |
WO2018119208A1 (en) | 2016-12-22 | 2018-06-28 | Global Blood Therapeutics, Inc. | Histone methyltransferase inhibitors |
WO2018226998A1 (en) * | 2017-06-09 | 2018-12-13 | Global Blood Therapeutics, Inc. | Azaindole compounds as histone methyltransferase inhibitors |
CA3188049A1 (en) * | 2018-04-25 | 2019-10-31 | Oncocross Co.,Ltd. | Composition for preventing and treating muscular disease |
CN113166058A (zh) | 2018-08-14 | 2021-07-23 | 奥斯特克有限公司 | 氟β-咔啉化合物 |
EP3836923B1 (en) | 2018-08-14 | 2024-10-16 | OssiFi Therapeutics LLC | Pyrrolo - dipyridine compounds for the treatment of bone loss |
WO2020072675A1 (en) | 2018-10-02 | 2020-04-09 | Northwestern University | Beta-carbolines as positive allosteric modulators of the human serotonin receptor 2c (5-ht2c) |
CN111374975A (zh) * | 2018-12-27 | 2020-07-07 | 北京大学 | 去氢骆驼蓬碱的药物用途 |
CN112047940B (zh) * | 2020-08-28 | 2021-06-29 | 南通大学 | 含1-(3,4-二甲氧基苯基)-β-咔啉单元的吡唑化合物的制备与用途 |
WO2024012554A1 (zh) * | 2022-07-14 | 2024-01-18 | 上海日馨医药科技股份有限公司 | Tpk激动剂及使用其治疗神经退行性疾病的方法 |
US11939330B1 (en) * | 2023-08-25 | 2024-03-26 | King Faisal University | Pyrido[3,4-b]indole-6-carboxylic acid compounds as CK2 inhibitors |
Family Cites Families (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE568675C (de) * | 1930-10-04 | 1933-01-27 | Boots Pure Drug Co Ltd | Verfahren zur Herstellung von O-Alkyl-, Oxyalkyl- oder Alkylaminoalkylaethern des Harmols oder Harmalols |
DK72180A (da) * | 1979-04-10 | 1980-10-11 | Ciba Geigy Ag | Fremgangsmaade til fremstilling af diazatricycler samt salte deraf |
DE3240514A1 (de) * | 1982-10-29 | 1984-05-03 | Schering AG, 1000 Berlin und 4709 Bergkamen | Ss-carboline, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische praeparate |
US4631149A (en) * | 1983-07-25 | 1986-12-23 | University Of Illinois | Antiviral eudistomins from a marine tunicate |
JPS63250378A (ja) * | 1987-04-07 | 1988-10-18 | Mitsubishi Kasei Corp | インド−ル誘導体 |
CA2140722A1 (en) | 1994-01-24 | 1995-07-25 | Joseph A. Jakubowski | Beta-carboline thromboxane synthase inhibitors |
DE4435477A1 (de) * | 1994-10-04 | 1996-04-11 | Bayer Ag | Cycloalkano-indol- und -azaindol-derivate |
US5532261A (en) * | 1994-12-12 | 1996-07-02 | Merck & Co., Inc. | Carbapenem antibiotics, compositions containing such compounds and methods of use |
JP2000516231A (ja) * | 1996-08-09 | 2000-12-05 | ベーリンガー インゲルハイム ファーマシューティカルズ インコーポレイテッド | 免疫調節物質としての4―置換β―カルボリン |
EP0827746B1 (en) * | 1996-09-05 | 2002-04-03 | Eli Lilly And Company | Carbazole analogues as selective beta3 adrenergic agonists |
US5843721A (en) | 1997-07-03 | 1998-12-01 | Tularik Inc. | Nucleic acids encoding human NIK protein |
ZA9810766B (en) * | 1997-11-28 | 1999-05-25 | Mochida Pharm Co Ltd | Novel compounds having cgmp-pde inhibitory activity |
DE19807993A1 (de) | 1998-02-26 | 1999-09-02 | Bayer Ag | Verwendung von ß-Carbolinderivaten zur Bekämpfung von TNF-alpha-abhängigen Krankheiten |
PL357284A1 (en) | 2000-03-15 | 2004-07-26 | Aventis Pharma Deutschland Gmbh | Substituted beta-carbolines with ikb-kinase inhibiting activity |
-
2001
- 2001-02-28 PL PL01357284A patent/PL357284A1/xx unknown
- 2001-02-28 AU AU3741801A patent/AU3741801A/xx active Pending
- 2001-02-28 AT AT01909799T patent/ATE465161T1/de not_active IP Right Cessation
- 2001-02-28 MX MXPA02007981A patent/MXPA02007981A/es active IP Right Grant
- 2001-02-28 SK SK1308-2002A patent/SK13082002A3/sk unknown
- 2001-02-28 JP JP2001567739A patent/JP5000828B2/ja not_active Expired - Fee Related
- 2001-02-28 CZ CZ20023031A patent/CZ301077B6/cs not_active IP Right Cessation
- 2001-02-28 EE EEP200200523A patent/EE200200523A/xx unknown
- 2001-02-28 CN CNB018064701A patent/CN100509810C/zh not_active Expired - Fee Related
- 2001-02-28 BR BR0109161-1A patent/BR0109161A/pt not_active IP Right Cessation
- 2001-02-28 DE DE60141895T patent/DE60141895D1/de not_active Expired - Lifetime
- 2001-02-28 KR KR1020027012072A patent/KR100826817B1/ko not_active IP Right Cessation
- 2001-02-28 AU AU2001237418A patent/AU2001237418B2/en not_active Ceased
- 2001-02-28 HU HU0300894A patent/HUP0300894A3/hu unknown
- 2001-02-28 CA CA002402549A patent/CA2402549A1/en not_active Abandoned
- 2001-02-28 IL IL15169501A patent/IL151695A0/xx unknown
- 2001-02-28 RU RU2002127682/04A patent/RU2277095C2/ru not_active IP Right Cessation
- 2001-02-28 NZ NZ521386A patent/NZ521386A/en unknown
- 2001-02-28 ME MEP-281/08A patent/MEP28108A/xx unknown
- 2001-02-28 YU YU65502A patent/YU65502A/sh unknown
- 2001-03-15 US US09/812,785 patent/US6627637B2/en not_active Expired - Lifetime
-
2002
- 2002-09-11 NO NO20024338A patent/NO324248B1/no not_active IP Right Cessation
- 2002-09-11 IL IL151695A patent/IL151695A/en not_active IP Right Cessation
- 2002-09-12 HR HR20020748A patent/HRP20020748A2/xx not_active Application Discontinuation
-
2003
- 2003-07-28 US US10/627,978 patent/US7026331B2/en not_active Expired - Lifetime
- 2003-09-09 HK HK03106409.9A patent/HK1054039B/zh not_active IP Right Cessation
-
2006
- 2006-03-28 US US11/390,287 patent/US7348336B2/en not_active Expired - Lifetime
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
SK13082002A3 (sk) | Substituované beta-karbolíny, spôsob ich prípravy a farmaceutické prostriedky, ktoré ich obsahujú | |
EP2262808B1 (en) | Chemokine receptor modulators | |
MXPA06013593A (es) | Nuevos derivados de piridazin-3(2h)-ona. | |
AU765128B2 (en) | Fused pyridopyridazine inhibitors of cGMP phosphodiesterase | |
AU2001237418A1 (en) | Substituted beta-carbolines with ikb-kinase inhibiting activity | |
EP1268477A1 (en) | Substituted beta-carbolines with ikb-kinase inhibiting activity | |
EP1209158A1 (en) | Substituted beta-carbolines | |
WO1995028387A1 (fr) | Compose benzamide et utilisation medicale dudit compose | |
JP2006506352A (ja) | Hivインテグラーゼ阻害剤として有用なジヒドロキシピリドピラジン−1,6−ジオン化合物 | |
EA002907B1 (ru) | Производные 6-фенилпиридил-2-амина, полезные в качестве ингибиторов nos | |
JP2003527394A5 (ru) | ||
JP2000119271A (ja) | 1h―イミダゾピリジン誘導体 | |
JP2007528394A (ja) | Hivインテグラーゼ阻害薬 | |
US4820710A (en) | Benzimidazole derivatives and pharmaceutical compositions containing them | |
EP1353905A2 (en) | Piperidine/piperazine-type inhibitors of p38 kinase | |
IL279452A (en) | History of pyrazole as MALT1 inhibitors | |
WO2002088122A1 (fr) | Composes heterocycliques | |
CA2578880A1 (en) | Pyrrolo[3,2-c]pyridine derivatives and processes for the preparation thereof | |
CZ265498A3 (cs) | Triazolové deriváty, způsob jejich výroby a farmaceutický prostředek s jejich obsahem | |
JPH0545591B2 (ru) | ||
ES2250750T3 (es) | Aroil piridinonas. | |
EP0461264A1 (en) | Ethynylphenyl derivative, production thereof, and remedy for diseases of circulatory organs containing the same as active ingredient | |
CZ155096A3 (en) | Aminoalkylaminopyridine derivatives, process of their preparation and pharmaceutical composition containing thereof | |
WO1998023607A1 (fr) | Derives de 1,4-dihydropyridine | |
JP2000239277A (ja) | イミダゾキナゾリン誘導体 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
FB9A | Suspension of patent application procedure |